Phosgene → (5R,7R)-7-(4-(3-(benzyloxy)prop-1-ynyl)phenyl)-3-oxa-1-azaspiro[4.4]nonan-2-one

HRID 1511855Notes

Reaction equation

HRID 1511855 reaction equation
[NH2:1][C@:2]1([CH2:24][OH:25])[CH2:6][CH2:5][C@@H:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]#[C:14][CH2:15][O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:9][CH:8]=2)[CH2:3]1.[OH-].[K+].[C:28](Cl)(Cl)=[O:29].CCOC(C)=O>C1(C)C=CC=CC=1.O>[CH2:17]([O:16][CH2:15][C:14]#[C:13][C:10]1[CH:11]=[CH:12][C:7]([C@@H:4]2[CH2:5][CH2:6][C@@:2]3([NH:1][C:28](=[O:29])[O:25][CH2:24]3)[CH2:3]2)=[CH:8][CH:9]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 6371PhosgeneHCID 8857Ethyl AcetateHCID 14797Potassium HydroxideHCID 57554621((1R,3R)-1-amino-3-(4-(3-(benzyloxy)prop-1-ynyl)phenyl)cyclopentyl)methanol

Product 1

HCID 57554650(5R,7R)-7-(4-(3-(benzyloxy)prop-1-ynyl)phenyl)-3-oxa-1-azaspiro[4.4]nonan-2-oneYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

To a solution of ((1R,3R)-1-amino-3-(4-(3-(benzyloxy)prop-1-ynyl)phenyl)cyclopentyl)methanol (25 g, 55.9 mmol) in toluene (200 mL) was added a solution of potassium hydroxide (12.54 g, 224 mmol) in water (40 mL) followed by a solution of 20% phosgene in toluene (41.5 g, 84 mmol). After about 4 hours EtOAc was added and the organic layer was separated and concentrated in vacuo. The crude product was purified by chromatography on silica gel (EtOAc/DCM) to provide (5R,7R)-7-(4-(3-(benzyloxy)prop-1-ynyl)phenyl)-3-oxa-1-azaspiro[4.4]nonan-2-one (20 g, 44.3 mmol, 79% yield) as a brown oil.

Workup

  1. customthe organic layer was separated
  2. concentrationconcentrated in vacuo
  3. customThe crude product was purified by chromatography on silica gel (EtOAc/DCM)

Sources & evidence

ORD record
ord-891a4d7f28af413c927242045007aa0b
Source dataset
uspto-grants-2012_07
Patent number
US08217027B2

Reaction notes

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